Genetic research is entering an exciting new phase, one in which comprehensive information about genetic variation can systematically be examined for association to medically important traits. Such studies will take many forms: hypothesis-driven examination of one or a few polymorphisms in vast clinical collections, studies of thousands of variants in candidate genes or regions of linkage, and genome-wide scans of hundreds of thousands of markers in each patient. Some will involve genotyping standard sets of variants, while others will require discovery of new variants and development of custom assays. In all cases a critical challenge is information systems to design experiments, manage millions of genotypes, and perform sophisticated analysis of correlations among variants, and between variants and disease phenotypes. We propose to create an NCRR Genotyping Center (GC) at the Broad Institute (BI), formerly the Whitehead/MIT Center for Genome Research. Our goal is to create a resource that will make it possible for any investigator to accomplish the four goals: (1) Design genotyping experiments using secure and confidential informatics tools for sample management, single nucleotide polymorphism (SNP) selection and discovery; (2) genotype selected Snips at high quality and throughput; (3) perform automated quality control and data management; and (4) to analyze data with rapidly evolving methods to study associations. Our application builds on over a decade's expertise at the Broad in the creation of high-throughput methods for genomic research, international projects to create public maps of genome sequence and variation, creation of analytic methods and software for genetic research, and discovery of genes for a human disease. Enabling broad access to genetic variation research requires more than genotyping: it requires combining a breadth of high-throughput technologies with innovative methods for data management and analysis. We aim to bridge this gap by combining the necessary range of technologies and advanced analytic tools in a single NCRR GC, and making them broadly available to investigators around the country.